Assessment of Retinopathy of Prematurity Regression and Reactivation Using an Artificial Intelligence–Based Vascular Severity Score
Authors: Sonja K. Eilts, Johanna M. Pfeil, Broder Poschkamp, Tim U. Krohne, Nicole Eter, Teresa Barth, Rainer Guthoff, Wolf Lagrèze, Milena Grundel, Marie-Christine Bründer, Martin Busch, Jayashree Kalpathy-Cramer, Michael F. Chiang, R. V. Paul Chan, Aaron S. Coyner, Susan Ostmo, J. Peter Campbell, Andreas Stahl, Milena Grundel, Johanna M Pfeil, Andreas Stahl, Marie-Christine Bründer, Anima Bühler, Moritz Daniel, Susanne Felzmann, Nicolai Gross, Stefanie Horn, Wolf A Lagrèze, Fanni Molnár, Claudia Müller, Sabine Reichl, Charlotte Reiff, Olga Richter, Milena Stech, Roland Hentschel, Dimitria Stavropolou, Juliane Tautz, Kerstin Bartsch, Jennifer Braunstein, Ralf Brinken, Christian Karl Brinkmann, Joanna Czauderna, Wiebke Dralle, Martin Gliem, Arno Goebel, Philipp Heymer, Martina Hofmann, Frank G Holz, Tim U Krohne, David Kupitz, Philipp Müller, Michael Petrak, Eva Janine Schmitz, Steffen Schmitz-Valckenberg, Moritz Schröder, Julia Steinberg, Julia Supé, Evelyn Kant, Diana Kunze, Andreas Müller, Adeline Adorf, Anne Alex, Florian Alten, Christoph R Clemens, Nicole Eter, Silvia Falkenau, Caroline Friedhoff, Desiree Sandra Loos, Natasa Mihailovic, Julia Termühlen, Constantin Uhlig, Isabell Hörnig-Franz, Esther Rieger-Fackeldey, Maria Tekaat, Claudius Werner, Mathias Altmann, Teresa Barth, Christiane Blecha, Sabine Brandl-Rühle, Horst Helbig, Karsten Hufendiek, Herbert Jägle, Julia Konrad, Eva Kopetzky, Fabian Lehmann, Isabel Oberacher-Velten, Annette Keller-Wackerbauer, Jochen Kittel, Hugo Segerer, Phillip Ackermann, Jemina Benga, Rainer Guthoff, Tanja Guthoff, Elena Kleinert, Ertan Mayatepek, Stefan Schrader, Magdalena Völker, Thomas Höhn, Klaus Lohmeier, Hemmen Sabir, Francisco Brevis, Tina Mönig, Simone Schwarz, Angela Ehmer, Synke Meltendorf, Claudia Schuart, Stefan Avenarius, Ralf Böttger, Christoph Apel, Anne Bergmann, Karsten Herrmann, Franziska Ockert-Schön, Sabine Wegener, Oliver Ehrt, Martin Nentwich, Angelika Pressler, Günther Rudolph, Orsolya Genzel-Boroviczeny, Susanne Schmidt, Hans-Georg Münch, Claude Thilmany, Sabine Aisenbrey, Anna Bruckmann, Spyridon Dimopoulos, Ulrike Hagemann, Werner Inhoffen, Michael Partsch, Merle Schrader, Daniela Süsskind, Michael Völker, Anja Bialkowski, Ingo Müller-Hansen, Andrea Gerberth, Heike Christine Hasselbach, Solveig Lindemann, Konstantine Purtskhvanidze, Yvonne Raffel, Johann Roider, Greta Schröder, Beke Szymanek, Jan Tode, Meike Bendiks, Simon Modlich, Isabel Jandeck, Heinrich Gerding, Lois E H Smith
Journal: JAMA Network Open (2023)

Importance One of the biggest challenges when using anti–vascular endothelial growth factor (VEGF) agents to treat retinopathy of prematurity (ROP) is the need to perform long-term follow-up examinations to identify eyes at risk of ROP reactivation requiring retreatment. Objective To evaluate whether an artificial intelligence (AI)–based vascular severity score (VSS) can be used to analyze ROP regression and reactivation after anti-VEGF treatment and potentially identify eyes at risk of ROP reactivation requiring retreatment. Design, Setting, and Participants This prognostic study was a secondary analysis of posterior pole fundus images collected during the multicenter, double-blind, investigator-initiated Comparing Alternative Ranibizumab Dosages for Safety and Efficacy in Retinopathy of Prematurity (CARE-ROP) randomized clinical trial, which compared 2 different doses of ranibizumab (0.12 mg vs 0.20 mg) for the treatment of ROP. The CARE-ROP trial screened and enrolled infants between September 5, 2014, and July 14, 2016. A total of 1046 wide-angle fundus images obtained from 19 infants at predefined study time points were analyzed. The analyses of VSS were performed between January 20, 2021, and November 18, 2022. Interventions An AI-based algorithm assigned a VSS between 1 (normal) and 9 (most severe) to fundus images. Main Outcomes and Measures Analysis of VSS in infants with ROP over time and VSS comparisons between the 2 treatment groups (0.12 mg vs 0.20 mg of ranibizumab) and between infants who did and did not receive retreatment for ROP reactivation. Results Among 19 infants with ROP in the CARE-ROP randomized clinical trial, the median (range) postmenstrual age at first treatment was 36.4 (34.7-39.7) weeks; 10 infants (52.6%) were male, and 18 (94.7%) were White. The mean (SD) VSS was 6.7 (1.9) at baseline and significantly decreased to 2.7 (1.9) at week 1 ( P &amp;amp;lt; .001) and 2.9 (1.3) at week 4 ( P &amp;amp;lt; .001). The mean (SD) VSS of infants with ROP reactivation requiring retreatment was 6.5 (1.9) at the time of retreatment, which was significantly higher than the VSS at week 4 ( P &amp;amp;lt; .001). No significant difference was found in VSS between the 2 treatment groups, but the change in VSS between baseline and week 1 was higher for infants who later required retreatment (mean [SD], 7.8 [1.3] at baseline vs 1.7 [0.7] at week 1) vs infants who did not (mean [SD], 6.4 [1.9] at baseline vs 3.0 [2.0] at week 1). In eyes requiring retreatment, higher baseline VSS was correlated with earlier time of retreatment (Pearson r = −0.9997; P &amp;amp;lt; .001). Conclusions and Relevance In this study, VSS decreased after ranibizumab treatment, consistent with clinical disease regression. In cases of ROP reactivation requiring retreatment, VSS increased again to values comparable with baseline values. In addition, a greater change in VSS during the first week after initial treatment was found to be associated with a higher risk of later ROP reactivation, and high baseline VSS was correlated with earlier retreatment. These findings may have implications for monitoring ROP regression and reactivation after anti-VEGF treatment.